title: Pleiotropic effect of lovastatin, with and without cholestyramine, in the post coronary artery bypass graft (Post CABG) trial.
abstract: This study evaluated patients in the Post Coronary Artery Bypass Graft (Post CABG) trial for evidence of statin pleiotropic effects in preventing atherosclerotic progression in saphenous vein grafts (SVGs). We studied 1,116 of the 1,351 patients in the Post CABG trial who were randomized to aggressive (low-density lipoprotein [LDL] cholesterol target <85 mg/dl) or moderate (target LDL cholesterol <140 mg/dl) lovastatin treatment and who had sufficient data available. The generalized estimating equation models, adjusting for important covariates, were applied to estimate the odds ratios (ORs) and probability of substantial atherosclerotic SVG progression (decrease in lumen diameter >or=0.6 mm) and the difference in minimum lumen diameter change between treatment groups. Aggressive lovastatin treatment compared with moderate treatment was associated with a significant decrease in risk of significant SVG atherosclerotic progression after adjustment for baseline cholesterol level, LDL cholesterol on treatment, high-density lipoprotein cholesterol, and triglyceride changes on treatment and other independent predictors (OR 0.68, 95% confidence interval 0.49 to 0.94, p = 0.019). Results were similar when the change or percent change from baseline of LDL cholesterol level on treatment was adjusted for rather than on-treatment LDL cholesterol and in the subset achieving a year-1 LDL cholesterol level from 90 to 135 mg/dl (OR 0.64, 95% confidence interval 0.42 to 0.98, p = 0.042). Mean decrease in minimum lumen diameter was also significantly smaller in the aggressive than the moderate treatment arm (-0.256 vs -0.343 mm, p = 0.042). In conclusion, aggressive versus moderate lovastatin treatment appeared therapeutic in slowing the atherosclerotic process in SVGs from Post CABG patients, independent of its greater LDL cholesterol-lowering effect.
authors.affiliation: Atherothrombosis and Coronary Artery Disease Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. domanskm@nhlbi.nih.gov
authors.forename: Michael
authors.initials: M
authors.lastname: Domanski
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.forename: Jerome
authors.initials: J
authors.lastname: Fleg
authors.forename: Sean
authors.initials: S
authors.lastname: Coady
authors.forename: Christine
authors.initials: C
authors.lastname: Gosen
authors.forename: Ruth
authors.initials: R
authors.lastname: Kirby
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Genell
authors.initials: G
authors.lastname: Knatterud
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000627:therapeutic use*; D017023:Coronary Angiography; D001026:Coronary Artery Bypass / Q000379:methods*; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D008148:Lovastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care / Q000379:methods*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002792:Cholestyramine Resin; D008148:Lovastatin